A SPECIFIC ANTIBODY ACTIVITY THAT NEUTRALIZES HIV INFECTIVITY IN VIVO

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

A SPECIFIC ANTIBODY ACTIVITY THAT NEUTRALIZES HIV INFECTIVITY IN VIVO

AIDS Vaccine Research and Clinical Trials. Putney SD and Bolognesi DP, eds. New York, Marcel Dekker, p. 369-78, 1990.. Unique Identifier : AIDSLINE ICDB/91676956
Emini EA; Dept. of Virus and Cell Biology, Merck Sharp and Dohme Res.; Laboratories, West Point, PA

Abstract: The task of developing a vaccine against HIV is complicated by a lack of fundamental knowledge concerning vaccine-relevant immune responses against the virus. The significance of the general anti-HIV responses elicited during persistent HIV infection remains a question. In vitro HIV-neutralizing antibody and favorable characteristics of the dominant neutralizing antibody species are reviewed, and studies by the author and associates on the in vivo protective efficacy of the dominant neutralizing antibody species are described. The antibody species directed against the dominant isolate-specific neutralization determinant appears to exhibit certain characteristics favoring its ability to act as a protective antibody in vivo. The neutralizing antibody species retains its ability to bind to virus after the virus has attached to its target cell. The antibody fully neutralizes HIV in vitro without an interactive period between virus and antibody prior to target cell addition. Four different purified antibody preparations were tested in experiments involving the in vitro interaction between neutralizing antibody and the challenge HIV followed by inoculation of the virus-antibody mixture into chimpanzees. Antibody preparations were (1) IgG from an HIV-infected chimpanzee, (2) a specific neutralizing monoclonal antibody (Mab) 0.5 beta, (3) IgG from an HIV-infected human, and (4) IgG from a normal, uninfected chimpanzee. Anti-HIV antibody activity was demonstrated by preparations 1 and 3, but not 4 (2 not done). Binding activity against the dominant neutralization determinant was observed with preparations 1 and 2, but not preparations 3 and 4. Following a 90-min incubation at room temperature, each of the virus-antibody mixtures was inoculated iv into a single chimpanzee. Anti-HIV activity was seen at 4-6 wk after inoculation in the two chimpanzees receiving nonneutralized virus (3 and 4), but the animal inoculated with virus previously neutralized by the polyclonal chimpanzee IgG exhibited no immunologic signs of HIV infection. A delayed, apparently low-level, infection developed in the chimpanzee inoculated with the Mab-neutralized virus. These results suggest that antibody to the isolate-specific dominant neutralization determinant can mediate at least some degree of in vivo protection. This ability, along with the ability of the antibody to rapidly neutralize the virus, supports the view that a successful HIV vaccine should incorporate the dominant neutralization determinant. (15 Refs)

Keywords: Animal Antibody Specificity/*IMMUNOLOGY Blotting, Western Chimpansee troglodytes Enzyme-Linked Immunosorbent Assay Gene Products, env/IMMUNOLOGY Gene Products, gag/IMMUNOLOGY Human HIV/*IMMUNOLOGY HIV Antibodies/*IMMUNOLOGY HIV Antigens/IMMUNOLOGY HIV Envelope Protein gp120/IMMUNOLOGY HIV Infections/*IMMUNOLOGY HIV-1/IMMUNOLOGY *Neutralization Tests Protein Precursors/IMMUNOLOGY Viral Core Proteins/IMMUNOLOGY Viral Vaccines/*IMMUNOLOGY MONOGRAPH
912130
M91C4086

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1991. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1991. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .